Field
The disclosure of the present application generally relates to drug delivery implants, and more specifically, drug delivery implants used to treat ocular conditions.
Description of the Related Art
Diabetic retinopathy is the leading cause of blindness among adults aged 20 to 74 years. It is estimated that 75,000 new cases of macular edema, 65,000 cases of proliferative retinopathy, and 12,000 to 24,000 new cases of blindness arise each year. Retinitis pigmentosa (RP) is a heterogeneous group of inherited neurodegenerative retinal diseases that cause the death of photoreceptor cells (rods and cones) that eventually leads to blindness. Glaucoma is a multifactorial optic neuropathy resulting from loss of retinal ganglion cells, corresponding atrophy of the optic nerve, and loss of visual function, which is manifested predominantly by visual field loss and decreased visual acuity and color vision. Geographic atrophy (“GA”) is one of 2 forms of the advanced stage of Age-Related Macular Degeneration (“AMD”). The advanced stage of AMD refers to that stage in which visual acuity loss can occur from AMD. Retinal detachments are a significant cause of ocular morbidity. There are 3 types of retinal detachment: rhegmatogenous, tractional, and exudative.
Brimonidine (5-bromo-6-(2-imidazolidinylideneamino) quinoxaline) is an alpha-2-selective adrenergic receptor agonist effective for treating open-angle glaucoma by decreasing aqueous humor production and increasing uveoscleral outflow. Brimonidine tartrate ophthalmic solution 0.2% (marketed as ALPHAGAN®) was approved by the US Food and Drug Administration (FDA) in September 1996 and in Europe in March 1997 (United Kingdom). Brimonidine tartrate ophthalmic solution with Purite® 0.15% and 0.1% (marketed as ALPHAGAN® P) was approved by the FDA in March 2001 and August 2005, respectively. These formulations are currently indicated for lowering IOP in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT).
A neuroprotective effect of brimonidine tartrate has been shown in animal models of optic nerve crush, moderate ocular hypertension, pressure-induced ischemia, and vascular ischemia. The neuroprotective effect of topical applications of brimonidine tartrate has also been explored clinically in patients with glaucoma, age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and acute non-arteritic anterior ischemic optic neuropathy. However, certain limitations exist with the use of brimonidine tartrate in intraocular implants.
For example, because of the size of the brimonidine tartrate molecule, the amount of drug that can be loaded into an implant may be limited. Also, the hydrophilic nature of brimonidine tartrate may limit the ability of the drug's use in sustained release formulations.